Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Kidney Int. 2011 Jul;80(1):88-92. doi: 10.1038/ki.2011.68. Epub 2011 Mar 23.
Recombinant human erythropoietin (r-HuEpo) has been used for the treatment of renal anemia. With the loss of its patent protection, there has been an upsurge of more affordable biosimilar agents, increasing patient access to treatment for these conditions. The complexity of the manufacturing process for these recombinant proteins, however, can result in altered properties that may significantly affect patient safety. As it is not known whether various r-HuEpo products can be safely interchanged, we studied 30 patients with chronic kidney disease treated by subcutaneous injection with biosimilar r-HuEpo and who developed a sudden loss of efficacy. Sera from 23 of these patients were positive for r-HuEpo-neutralizing antibodies, and their bone marrow biopsies indicated pure red-cell aplasia, indicating the loss of erythroblasts. Sera and bone marrow biopsies from the remaining seven patients were negative for anti-r-HuEpo antibodies and red-cell aplasia, respectively. The cause for r-HuEpo hyporesponsiveness was occult gastrointestinal bleeding. Thus, subcutaneous injection of biosimilar r-HuEpo can cause adverse immunological effects. A large, long-term, pharmacovigilance study is necessary to monitor and ensure patient safety for these agents.
重组人促红细胞生成素（r-HuEpo）已被用于治疗肾性贫血。随着其专利保护的失效，更多价格实惠的生物类似药如雨后春笋般涌现，增加了患者获得这些疾病治疗的机会。然而，这些重组蛋白的制造过程非常复杂，可能会导致其性质发生改变，从而严重影响患者的安全。由于尚不清楚不同的 r-HuEpo 产品是否可以安全地相互替代，我们研究了 30 名接受生物类似 r-HuEpo 皮下注射治疗的慢性肾脏病患者，他们突然出现疗效丧失。其中 23 名患者的血清呈 r-HuEpo 中和抗体阳性，骨髓活检显示纯红细胞再生障碍，表明红细胞生成减少。其余 7 名患者的血清和骨髓活检分别呈抗 r-HuEpo 抗体阴性和红细胞再生障碍。r-HuEpo 低反应的原因是隐匿性胃肠道出血。因此，皮下注射生物类似 r-HuEpo 可引起免疫相关不良事件。需要进行大规模、长期的药物警戒研究，以监测和确保这些药物的患者安全。
